Does this patient have polymyalgia rheumatica?

Polymyalgia rheumatica (PMR) is typically described as pain and stiffness in the hips and shoulders. PMR is a disease of older adults; the mean age of onset is 70 years, and it almost never occurs in patients younger than 50 years.

As with many inflammatory rheumatic diseases, the stiffness associated with polymyalgia rheumatica is worst in the early morning; patients may note physical difficulty getting out of bed in the morning. Some patients describe that they have to perform a "logroll" (i.e., roll out of bed, without bending at the hips) to get out of bed in the morning. The stiffness resolves during the day, and many patients will note that they can function normally in the late afternoon.

Since most patients will not be evaluated in the early morning, many will be relatively asymptomatic at the time of their clinic appointment, and the diagnosis will need to be established based on the patient's history. True muscle weakness is not a component of PMR, and should trigger an evaluation for neurologic disorders. Because of potential overlap in the clinical phenotypes, the possibility of rheumatoid arthritis should be considered when evaluating a patient for PMR.

PMR may be one of the few disorders in rheumatology that may be diagnosed based on response to treatment: most patients will have a dramatic improvement within 1 day to low dose prednisone. Failure to observe a rapid improvement should trigger consideration of other diagnoses (such as giant cell arteritis or paraneoplastic myalgias).

Ten percent of patients with PMR will develop clinical giant cell arteritis at some point. One study demonstrated that among patients thought to have PMR alone, 8% of patients had ultrasound evidence of active temporal arteritis, demonstrating the close overlap between these diagnoses.

Fifty percent of patients with giant cell arteritis will have PMR; in these cases, the symptoms will often need to be treated with several days of high dose glucocorticoid therapy before symptomatic relief is achieved.

When evaluating a patient for a diagnosis of PMR, the clinician must simultaneously consider the possibility of rheumatoid arthritis, adhesive capsulitis (and other shoulder disorders), and giant cell arteritis, particularly for patients with an incomplete response to glucocorticoids.

Rheumatoid arthritis is approximately 100-fold more common than polymyalgia rheumatica; it is therefore worth considering in any patient with frank synovitis. The presence of an anti-citrullinated protein antibody (ACPA) such as anti-cyclic citrullinated peptide antibody (anti-CCP) strongly favors a diagnosis of rheumatoid arthritis in such cases.

Adhesive capsulitis of the shoulder is a common condition that, like PMR, is also associated with pain and decreased range of motion. Unlike PMR, however, the associated pain is worse at night, and the pain associated with adhesive capsulitis may be self-limited.

Any patient evaluated for PMR should be simultaneously evaluated for the possibility of giant cell arteritis. The presence of visual changes, carotidynia, jaw claudication, arm claudication, temporal headache, scalp tenderness, or dry cough should lead to serious consideration of temporal artery biopsy or imaging of the aorta to look for further evidence of giant cell arteritis.

Patients with malignancy often experience musculoskeletal pain as a paraneoplastic phenomenon, and patients who fail to respond to glucocorticoid therapy, but do not appear to have one of the alternate diagnoses mentioned above, should undergo age-appropriate screening for malignancy.

What tests to perform?

Lab testing

Acute phase reactants (such as an ESR and CRP) are generally ordered as part of the evaluation of polymyalgia rheumatica. Other laboratory signs of inflammation may include: thrombocytosis, leukocytosis, anemia, hypoalbuminemia, polyclonal hypergammaglobulinemia, and an elevated ferritin.

While these tests may confirm the presence of an inflammatory disorder (such as polymyalgia rheumatica), these are not specific for this diagnosis. These lab tests may be elevated in other rheumatic diseases (such as giant cell arteritis), malignancy, and infection.

Although PMR is associated with HLA-DBR1*04, this test is not routinely performed.

Imaging

Although PMR may initially be asymmetric, patients complaining of symptoms affecting just one shoulder or one hip may require imaging (such as an MRI) to confirm that the patient's symptoms are not due to trauma, which is relatively common among older patients.

Imaging is otherwise not routinely performed as part of the evaluation of patients with polymyalgia rheumatica, although MRI, PET, and ultrasound in research studies have demonstrated bursitis and tendonitis in patients with PMR.

Approximately 10% of patients with active polymyalgia rheumatica have a normal ESR despite having active disease. Complete lack of any serologic evidence of inflammation in a patient who does not carry a prior diagnosis of PMR, however, should trigger a thorough evaluation for other etiologies, especially if the patient's response to low-dose prednisone therapy is not immediate and robust.

Biopsy

If there is concern for giant cell arteritis, it is prudent to obtain a temporal artery biopsy, or imaging for aortitis. Magnetic resonance imaging may be particularly useful to evaluate for aortitis, since it may reveal evidence of vessel wall enhancement or edema that may be difficult to detect using other modalities. Ultrasound of the temporal arteries is widely used in Europe to establish a diagnosis of giant cell arteritis, but most American centers lack the expertise to use ultrasound as a replacement for temporal artery biopsy.

Biopsy otherwise plays no role in the evaluation of patients with polymyalgia rheumatica.

Overall interpretation of test results (diagnosis, prognosis)

Typically, acute phase reactants and imaging are used to make a diagnosis of polymyalgia rheumatica; after the initial diagnosis is established, the value of following acute phase reactants serially over time is less clear, particularly among patients who are doing well clinically. Acute phase reactants may increase modestly with glucocorticoid taper, and this is not necessarily indicative of a disease flare.

The prognosis associated with polymyalgia rheumatica is excellent, although many patients will require maintenance therapy with low dose prednisone for several years or longer.

How should patients with polymyalgia rheumatica be managed?

In 2015, the American College of Rheumatology and the European League Against Rheumatism published guidelines that suggest starting patients on prednisone 12.5 mg-25 mg daily. Lower starting doses of steroid are associated with lower remission rates; higher doses of steroid are associated with a higher rate of glucocorticoid-associated complications without increasing the therapeutic response.

Patients should note a substantial improvement in symptoms within the first 24 hours of therapy; failure to observe a dramatic improvement should bring the diagnosis of polymyalgia rheumatica into question. It may be worthwhile to increase the starting dose of prednisone up to 20 mg, or to split the prednisone into twice daily dosing, in patients with an incomplete response to steroid therapy.

After an appropriate therapeutic response has been observed, the dose of prednisone should be maintained for 2-4 weeks, after which time prednisone may be lowered by 1 mg/month.

Not all patients will manage to taper completely off of prednisone; many patients will develop myalgias, which may represent recurrent polymyalgia rheumatica or adrenal insufficiency, and may require low-dose prednisone for remission maintenance therapy.

Recurrence is not uncommon, and will respond to prednisone. In patients who are at high risk for prednisone-associated side effects, it may be reasonable to add methotrexate (and folate) to the patient's regimen as a steroid-sparing regimen, although the data supporting the use of methotrexate for polymyalgia rheumatica are weak. More recently, there has also been interest in using tocilizumab for the treatment of polymyalgia rheumatica, as well.

What happens to patients with polymyalgia rheumatica?

PMR has a prevalence of 700 per 100,000 patients older than 50. The disease tends to affect women more than men, and is more common among patients of northern European descent. Because of the overlap between these conditions, patients presenting with polymyalgia rheumatica should also be evaluated for the possibility of giant cell arteritis.

The prognosis associated with PMR in the absence of giant cell arteritis is quite good, and should not be associated with permanent debility; although some patients may need to remain on low-dose prednisone therapy for several years or longer.

Prednisone, even at low doses, may be associated with an increased risk of cataracts, glaucoma, accelerated coronary artery disease, skin fragility, osteoporosis, and mood swings, which should be evaluated and treated as appropriate.

How to utilize team care?

Specialty consultations

It is not uncommon for patients with polymyalgia rheumatica to have other reasons for hip or shoulder discomfort, and some patients may benefit from evaluation by an orthopedic surgeon or physiatrist if one suspects that a structural problem may be present. This may become more apparent after the initial treatment phase, when the patient is left with asymmetric complaints.

Nurses

Older patients may have difficulty with medical compliance, and nurses may be helpful to teach patients strategies to ensure compliance (such as pill boxes with compartments for every day of the week, which may be filled weekly, in advance). Nurses may also help evaluate the patient for hyperglycemia, which may be associated with prednisone use.

Pharmacists

Prednisone has relatively few drug interactions, but for patients who are maintained on low dose prednisone for long periods of time, the risk of side-effects is presumably cumulative, and pharmacists may wish to remind patients to continue with regular screening for eye, bone, and cardiovascular health.

Dieticians

Prednisone predisposes to hyperglycemia and diabetes, and teaching patients how to avoid foods with a high glycemic index is invaluable to prevent complications of therapy.

Therapists

In cases of debility, physical therapists may be very helpful to help patients build back lost muscle mass (due to inactivity, and the direct effect of prednisone on the muscle).

Are there clinical practice guidelines to inform decision making?

In 2012, the American College of Rheumatology (ACR) and the European League against Rheumatic Disease (EULAR) released provisional criteria for the classification of polymyalgia rheumatica. Using these criteria, a patient must be at least 50 years old, have bilateral shoulder pain, and abnormal acute phase reactants, in order to be classified as having polymyalgia rheumatica.

The 2012 criteria employ a point system, in which patients must have a score of at least four to be classified as having PMR. Two points are associated with morning stiffness lasting longer than 45 minutes, or the absence of a rheumatoid factor or anti-citrullinated peptide antibody. One point is awarded for the presence of hip pain (or limited range of motion), or the absence of other joint involvement.

For example, a 50 year old man with bilateral shoulder pain who complains of morning stiffness lasting for 1 hour, and an elevated ESR, but negative rheumatoid factor and ACPA, may be classified as having polymyalgia rheumatica

The criteria are designed to exclude patients who may have adhesive capsulitis of the shoulder or rheumatoid arthritis, both of which are common. The criteria, therefore, exclude patients with unilateral shoulder involvement or normal acute phase reactants, who clinically have PMR.

It is important to remember that these are classification criteria (designed to identify a homogenous patient population for clinical trials) and not diagnostic criteria. Therefore, failure to meet these criteria does not indicate that a given patient does not have PMR. Similarly, some patients who meet these classification criteria may have an alternate diagnosis.